Category: 59973-80-7

Andrews, Peter published the artcileA comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro, Recommanded Product: Sulindac sulfone, the publication is Cancer Chemotherapy and Pharmacology (2008), 61(2), 203-214, database is CAplus and MEDLINE.

Previously, we reported in vitro observations suggesting that ibuprofen is an effective non-prescription non-steroidal anti-inflammatory drug (NSAID) to reduce the survival of human prostate cancer cells (Andrews et al. in Cancer Chemother Pharmacol 502:77-284, 2002), and that this observed effectiveness is mediated by an up-regulation of the p75^NTR tumor suppressor (Khwaja et al. in Cancer Res 646:207-6213, 2004). However, other NSAIDs and their derivatives have received significant attention with regard to their anti-cancer effectiveness and have been selected for clin. trials to treat a variety of human cancers. In this investigation, we compared celecoxib, sulindac sulfone, nitric oxide linked NSAIDs, and R-flurbiprofen with ibuprofen in their ability to inhibit the growth of a variety of human cancer cells lines including cells lines with multi-drug resistance. We also evaluated whether, like ibuprofen, an up-regulation of p75^NTR is a mol. mechanism that mediates the anti-growth effectiveness of these drugs. Selected dosages for each drug were evaluated for their ability to reduce the growth (MTT anal.) and induce apoptosis (Hoechst staining) of a variety of different cancer cell lines, including an ovarian cell line expressing multidrug resistance-1 glycoprotein (MDR-1). The drugs were then analyzed using immunoblot, RT-PCR and siRNA to study the role of p75^NTR in their anti-growth effectiveness. This study revealed consistency in the drug dosages that inhibit the survival of different human cancer cell lines. While NO-linked aspirin and celecoxib were most effective in decreasing cell growth and inducing apoptosis at the lowest dosages, R-flurbiprofen and ibuprofen were most effective at clin. relevant dosages. A multidrug resistant ovarian cell line is more resistant to growth inhibition by the drugs tested than its non-drug resistant parental counterpart. There was no correlation between the expression of cyclooxygenase-2 (COX-2) and the ability of the drugs to reduce cancer cell survival. All the drugs tested induced an up-regulation in p75^NTR tumor suppressor gene expression in concert with their observed growth inhibiting ability. Inhibition of p75^NTR expression with siRNA reduced the cell growth inhibiting effects of all the drugs tested. The method of chemotherapy (i.e., intravascular, intrathecal, oral) might dictate the choice of NSAID/NSAID derivative used to treat/prevent a given type of cancer. Also, the p75^NTR tumor suppressor appears to be a common mol. mechanism that mediates the growth inhibiting effectiveness of these drugs.

Cancer Chemotherapy and Pharmacology published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Recommanded Product: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Pusztai, Lajos published the artcilePhase I and II study of exisulind in combination with capecitabine in patients with metastatic breast cancer, Name: Sulindac sulfone, the publication is Journal of Clinical Oncology (2003), 21(18), 3454-3461, database is CAplus and MEDLINE.

We studied the safety and clin. activity of exisulind in combination with capecitabine in 35 patients with metastatic breast cancer (MBC). All patients had received previous anthracycline and taxane chemotherapies. Two dose levels of exisulind were explored, 125 and 250 mg orally bid as continuous daily therapy, concomitant with capecitabine 2,000 mg/m² for 14 days in 21-day cycles. In the phase I study, the dose-limiting toxicities were hand-foot syndrome and diarrhea. The 125-mg bid dose was selected for phase II testing. The most common nonhematol. grade 2 to 3 adverse events were hand-foot syndrome (57%) and fatigue (48%). The most frequent grade 2 to 3 laboratory abnormality was granulocytopenia. No death, unexpected adverse events, or cumulative toxicity were encountered. One complete and four partial responses were achieved (objective response rate, 16%) in the 31 patients assessable for response. The median duration of response was 31 wk; three patients experienced stable disease longer than 26 wk. Overall clin. benefit (complete response, partial response, or stable disease > 26 wk) was 23%. Fourteen specimens were available for immunohistochem. assessment of phosphodiesterase-5 isoenzyme (PDE-5) and PDE-2 expression, which are the targets of exisulind. Eighty percent of tumors showed some expression of PDE-5 in the invasive cancer cells including 35% that showed moderate or strong staining. PDE-2 showed moderate or strong staining in 78% of tumors. There was no apparent association between tumor response and staining intensity. Exisulind (125 mg orally bid) in combination with capecitabine is well tolerated and the combination has anticancer activity similar to that of capecitabine alone in heavily pretreated patients with MBC.

Journal of Clinical Oncology published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Name: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Ashour, Abdelkader E. published the artcilePhosphodiesterase-5 inhibitors in the management of cancer, Synthetic Route of 59973-80-7, the publication is Asian Journal of Biomedical and Pharmaceutical Sciences (2013), 3(20), 1-5, 5 pp., database is CAplus.

A review. Selective phosphodiesterase type-5 (PDE5) inhibitors such as sildenafil, vardenafil and tadalafil are commonly used first-line therapy for erectile dysfunction (ED). The safety and high tolerability of these drugs has garnered substantial interest among researchers to investigate further beneficial nonerectogenic uses for such drugs. PDE5 expression has shown to be increased in several human malignancies, suggesting that this enzyme may play a role in tumorigenesis. This is supported by the reported anticancer activity of PDE5 inhibitors such as exisulinde and its analogs, as well as vardenafil. Further, PDE5 inhibitors have recently been reported to sensitize certain types of cancer to standard chemotherapeutic drugs. The aim of this review is to shed some light on the existing preclin. evidence supporting the use of PDE5 inhibitors as potential effective adjuncts in cancer chemotherapy and even as anticancer agents. I also showed our recent unpublished data with regard to the promising antitumor activity of vardenafil, a potent PDE5 inhibitor, against brain cancer.

Asian Journal of Biomedical and Pharmaceutical Sciences published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Synthetic Route of 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Wu, Zhufeng published the artcileEstablishment of pharmacophore and VolSurf models to predict the substrates of UDP-glucuronosyltransferase1A3, Formula: C20H17FO4S, the publication is Xenobiotica (2015), 45(8), 653-662, database is CAplus and MEDLINE.

1. UDP-glucuronosyltransferase1A3 (UGT1A3) catalyzes glucuronidation of numerous xenobiotics/drugs. Here, we aimed to establish substrate selectivity models for UGT1A3 using the pharmacophore and VolSurf approaches. 2. Fifty structurally diverse substrates of UGT1A3 were collated from the literature. These substrates were divided into training (n = 34) and test sets (n = 16). The pharmacophore model was developed using the Discovery Studio 2.5 software. A user-defined feature (i.e. the glucuronidation site) was included in the program for model generation. The VolSurf model was derived using the VolSurf program implemented in SYBYL 8.0 software. 3. The pharmacophore model consisted of three features (i.e. one glucuronidation site and two hydrogen-bond acceptors). The activities of 81% of test set substrates were adequately predicted (deviated by less than one-log unit) by the model, suggestive of a satisfactory predictive power. The refined VolSurf model based on 22 mol. descriptors was statistically significant (r² = 0.793, q² = 0.606). It also processed a good predictability as the activities of 14 test set compounds were well predicted. The VolSurf model highlighted the chem. features (including large mol. size, hydrophilic regions and hydrogen-bonding groups) contributing to favored glucuronidation by UGT1A3. 4. In conclusion, two predictive 3D-QSAR models (i.e. the pharmacophore and VolSurf models) for UGT1A3 were successfully established. These models contributed to an improved understanding of the substrate preference of UGT1A3 and a more comprehensive prediction of UGT-mediated metabolism

Xenobiotica published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C38H24F4O4P2, Formula: C20H17FO4S.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Zheng, Xuehua published the artcileThe molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase, Safety of Sulindac sulfone, the publication is FEBS Letters (2012), 586(1), 55-59, database is CAplus and MEDLINE.

Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clin. effects on Type 2 diabetes. However, the mol. basis for these properties is unclear. Here, we report that SLD and its pharmacol. active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallog. anal. reveals that π-π stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

FEBS Letters published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C13H24INO4, Safety of Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Liu, Xiangguo published the artcileDeath Receptor Regulation and Celecoxib-Induced Apoptosis in Human Lung Cancer Cells, Name: Sulindac sulfone, the publication is Journal of the National Cancer Institute (2004), 96(23), 1769-1780, database is CAplus and MEDLINE.

Background: Celecoxib, a cyclooxygenase 2 inhibitor, has chemopreventive and therapeutic activities toward lung cancer and other epithelial malignancies. Celecoxib can induce apoptosis in various cancer cell lines through a mechanism that is independent of its cyclooxygenase 2 inhibitory activity but is otherwise largely uncharacterized. We investigated the mechanism of celecoxib-induced apoptosis further. Methods: All experiments were conducted in human non-small-cell lung carcinoma (NSCLC) cell lines; results in celecoxib-treated and untreated cells were compared. Cell survival was assessed with a sulforhodamine B assay. Apoptosis was assessed by DNA fragmentation with an ELISA, by terminal deoxynucleotidyltransferase-mediated dUTP nick-end-labeling (TUNEL) assay, and by western blot anal. of caspase activation. Death receptor gene and protein expression was detected by northern and western blot anal., resp. Gene silencing was achieved with small interfering RNA (siRNA) technol. Results: Celecoxib treatment decreased cell survival, activated caspase cascades, and increased DNA fragmentation, all of which were abrogated when caspase 8 expression was silenced with caspase 8 siRNA. Celecoxib treatment induced the expression of death receptors, particularly that of DR5. Overexpression of a dominant neg. Fas-associated death domain mutant, but not of BCL2, reduced the level of celecoxib-induced apoptosis, and silencing of DR5 expression by DR5 siRNA suppressed celecoxib-induced caspase 8 activation and apoptosis. Combination treatment with celecoxib and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced addnl. apoptosis. For example, survival of A549 cells was decreased with 50 μM celecoxib alone by 38.7% (95% confidence interval [CI] = 35.2% to 42.2%), with TRAIL alone by 29.3% (95% CI = 25.1% to 33.6%), but with their combination by 77.5% (95% CI = 74.5% to 79.5%), a greater than additive effect. Conclusion: Celecoxib appears to induce apoptosis in human NSCLC through the extrinsic death receptor pathway.

Journal of the National Cancer Institute published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Name: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Kim, Ju-Young published the artcileActivation of Protein Kinase G (PKG) Reduces Neointimal Hyperplasia, Inhibits Platelet Aggregation, and Facilitates Re-endothelialization, Related Products of naphthyridine, the publication is Scientific Reports (2016), 36979, database is CAplus and MEDLINE.

In spite of its great success in reducing restenosis, drug-eluting stent (DES) has unfavorable aspects such as stent thrombosis and delayed re-endothelialization. We examined the effects of PKG activation by Exisulind on neointimal formation, platelet aggregation, and re-endothelialization. Exisulind significantly reduced VSMCs viability, cell cycle progression, migration, and neointimal hyperplasia after vascular injury in rat carotid arteries. Interestingly, in contrast to the effect on VSMC viability, Exisulind did not reduce the viability of endothelial cells. Increased PKG activity by Exisulind inhibited PDGF-stimulated phenotype change of VSMCs from a contractile to a synthetic form. Conversely, the use of PKG inhibitor or gene transfer of dominant-neg. PKG reversed the effects of Exisulind, resulting in the increased viability of VSMCs and neointimal formation. In addition, Exisulind facilitated the differentiation of peripheral blood mononuclear cells to endothelial lineage via PKG pathway, while inhibiting to VSMCs lineage, which was correlated with the enhanced re-endothelialization in vivo. Finally, Exisulind reduced platelet aggregation, which was mediated via PKG activation. This study demonstrated that Exisulind inhibits neointimal formation and platelet aggregation while increasing re-endothelialization via PKG pathway. These findings suggest that Exisulind could be a promising candidate drug of DES for the prevention of restenosis without other complications.

Scientific Reports published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Related Products of naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Deguchi, Atsuko published the artcileActivation of Protein Kinase G Up-regulates Expression of 15-Lipoxygenase-1 in Human Colon Cancer Cells, Category: naphthyridine, the publication is Cancer Research (2005), 65(18), 8442-8447, database is CAplus and MEDLINE.

Recent studies indicate that the induction of apoptosis in human colon cancer cells by certain nonsteroidal anti-inflammatory drugs involves increased expression of 15-LOX-1 and synthesis of its major product 13-S-hydroxyoctadecadienoic acid (13-S-HODE). Evidence was obtained that this occurs via a cyclooxygenase-2 (COX-2)-independent mechanism, but the actual mechanism of induction of 15-LOX-1 by these compounds is not known. There is extensive evidence that treatment of SW480 human colon cancer cells with sulindac sulfone (Exisulind, Aptosyn) or the related derivative OSI-461, both of which inhibit cGMP-phosphodiesterases but lack COX-2 inhibitory activity, causes an increase in intracellular levels of cGMP, thus activating protein kinase G (PKG), which then activates pathways that lead to apoptosis. Therefore, in the present study, the authors examined the effects of various agents that cause increased cellular levels of cGMP on the expression of 15-LOX-1 in SW480 human colon cancer cells. Treatment of the cells with Exisulind, sulindac sulfide, OSI-461, the guanylyl cyclase activator YC-1, or the cell-permeable cGMP compound 8-para-chlorophenylthio-cGMP (8-pCPT-cGMP) caused an increase in cellular levels of 15-LOX-1. Exisulind, OSI-461, and 8-pCPT-cGMP also increased mRNA levels of 15-LOX-1, suggesting that the effects were at the level of transcription. The cGMP-phosphodiesterase inhibitors and YC-1 increased the production of 13-S-HODE, which is the linoleic acid metabolite of 15-LOX-1. Treatment of SW480 cells with the PKG inhibitor R_p-8-pCPT-cGMP blocked Exisulind-induced 15-LOX-1 expression. Furthermore, derivatives of SW480 cells that were engineered to stably overexpress wild-type PKG Iβ displayed increased cellular levels of 15-LOX-1 when compared with vector control cells. Taken together, these results provide evidence that the cGMP/PKG pathway can play an important role in the induction of 15-LOX-1 expression by nonsteroidal anti-inflammatory drugs and related agents.

Cancer Research published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Category: naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Sheng, Huaming published the artcileIdentification of the Sulfone Functionality in Protonated Analytes via Ion/Molecule Reactions in a Linear Quadrupole Ion Trap Mass Spectrometer, Safety of Sulindac sulfone, the publication is Journal of Organic Chemistry (2014), 79(7), 2883-2889, database is CAplus and MEDLINE.

A tandem mass spectrometric method is presented for the rapid identification of drug metabolites that contain the sulfone functional group. This method is based on a gas-phase ion/mol. reaction of protonated sulfone analytes with tri-Me borate (TMB) that yields a diagnostic product ion, adduct-Me₂O, at high reaction efficiency. A variety of compounds with different functional groups, such as sulfoxides, hydroxylamines, N-oxides, anilines, phenol, an aliphatic amine, and an aliphatic alc., were examined to probe the selectivity of this reaction. Except for protonated sulfones, most of the protonated compounds react very slowly or not at all with TMB. Most importantly, none of them give the adduct-Me₂O product. A mechanism that explains the observed selectivity is proposed for the diagnostic reaction and is supported by quantum chem. calculations The reaction was tested with the anti-inflammatory drug sulindac and its metabolite, sulindac sulfone, which were readily distinguished. The presence of other functionalities in addition to sulfone was found not to influence the diagnostic reactivity.

Journal of Organic Chemistry published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H28B2O4S2, Safety of Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Allani, S. K. published the artcileSulindac induces differentiation of glioblastoma stem cells making them more sensitive to oxidative stress, Category: naphthyridine, the publication is Neoplasma (2018), 65(3), 376-388, database is CAplus and MEDLINE.

Glioblastoma tumors (GBM) are very heterogeneous, being comprised of several cell subtypes, including glioblastoma stem cells (GSC). These tumors have a high rate of recurrence after initial treatment and one of the most prevalent theories to explain this is the cancer stem cell theory, which proposes that glioblastomas arise from mutations that transform normal neural stem cells (NSC) into GSC, which are highly resistant to oxidative stress and anti-cancer therapies. To study the effect of sulindac on both normal and cancer stem cells, we have isolated normal neural stem cells (NSC), from mice hippocampi and glioblastoma stem cells (GSC) from a glioma cell line, U87. As expected from previous studies sulindac can protect normal astrocytes against oxidative stress. Sulindac induces differentiation of both NSC and GSC cells and sulindac upregulates neurogenesis in NSC. The differentiated NSC are also protected from oxidative stress damage, whereas the differentiation of GSC by sulindac increases the sensitivity of these cells to agents that cause oxidative stress. The S epimer of sulindac is more effective than the R epimer in inducing neuronal differentiation in both NSC and GSC. These results indicate that the ability of sulindac to induce GSC differentiation may have therapeutic value in preventing tumor recurrence.

Neoplasma published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Category: naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem